Glycogen synthase kinase 3beta in the nucleus accumbens core is critical for methamphetamine-induced behavioral sensitization

摘要

As a ubiquitous serine/threonine protein kinase, glycogen synthase kinase 3p (GSK-3beta) has been considered to be important in the synaptic plasticity that underlies dopamine-related behaviors and diseases. We recently found that GSK-3p activity in the nucleus accumbens (NAc) core is critically involved in cocaine-induced behavioral sensitization. The present study further explored the association between the changes in GSK-3beta activity in the NAc and the chronic administration of methamphetamine. We also examined whether blocking GSK-3beta activity in the NAc could alter the initiation and expression of methamphetamine (1 mg/kg, i.p.)-induced locomotor sensitization in rats using systemic administration of lithium chloride (LiCI, 100 mg/kg, i.p) and brain region-specific administration of the GSK-3beta inhibitor SB216763 (1 ng/side). We found that GSK-3P activity increased in the NAc core, but not NAc shell, after chronic methamphetamine administration. The initiation and expression of methamphetamine-induced locomotor sensitization was attenuated by systemic administration of LiCI and direct infusion of SB216763 into the NAc core, but not NAc shell. These results indicate that GSK-3P activity in the NAc core mediates the initiation and expression of methamphetamine-induced iocomotor sensitization, suggesting that GSK-3beta may be a potential target for the treatment of psychostimuiant addiction.